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Chapter 27

Viruses

1

http://onlyhdwallpapers.com/high-definition-wallpaper/viruses-you-now-all-have-swine-flu-high-resolution-desktop-hd-wallpaper-297337/

Nature of Viruses

• All viruses have same basic structure • Nucleic acid core surrounded by capsid

• Can be DNA or RNA

• Circular or linear

• Single or double stranded

• No cytoplasm – not a cell • No ribosomes

• Classified by genome, in part • RNA viruses, DNA viruses, or retroviruses

2 http://www.biologyjunction.com/virus_notes_b1.htm

• Virion - single virus particle outside of a cell • Not alive or dead • Relies on living cells for replication

• Capsid - nearly all viruses form a protein sheath around their nucleic acid core • Composed of repeats of 1 to a few

proteins

• Some viruses store specialized enzymes not found in host – Example is Reverse transcriptase

not found in host

• Many animal viruses have an envelope • Derived from host cell membrane

with viral proteins

3 http://www.epidemic.org/thefacts/viruses/retroviruses/

Structure of a

retrovirus

http://www.abovetopsecret.com/forum/thread926524/pg1

Viral Shapes

• Most viruses come in two simple shapes

• Helical – TMV, rodlike or threadlike

• Icosahedral – soccer ball shape

• Some viruses are more complex • T-even bacteriophages – 2 fold symmetry

• Bacteriophages are viruses that infect bacteria

• Poxviruses – multilayered capsid

• Enveloped viruses are polymorphic

4

Viral hosts

• Viruses are obligate intracellular parasites in every kind of organism investigated – Bacteria to multicellular eukaryotes

• Host range – types of organisms infected – Each type of virus has a limited host range – Tissue tropism – inside a host the virus

may only infect certain tissues

• Viruses can remain dormant or latent for years – Chicken pox can reemerge as shingles

• More kinds of viruses exist than organisms

9 http://health.howstuffworks.com/skin-care/problems/medical/chicken-pox1.htm

Viral Replication

• Infecting virus can be thought of as a set of instructions

• Viral genome uses host cell’s “machinery” into making more viruses

• Viruses can only reproduce inside cells

– Outside, they are metabolically inert virions

10 http://science.howstuffworks.com/life/cellular-microscopic/virus-human2.htm

• Viruses lack their own ribosomes and enzymes for protein and nucleic acid synthesis

• Virus hijacks the cell’s transcription and translation machineries to express – Early genes – neutralize defenses,

breaks down host DNA – Middle genes – mobilizes

transcription/translation – Late genes – assembles and releases

viruses

• End result is assembly and release of viruses

11 http://www.microbiologybytes.com/virology/Polyomaviruses.html

Viral Genomes

• Vary greatly in both type of nucleic acid and number of strands

• DNA or RNA

• Single or double stranded

14 http://www.mansfield.ohio-state.edu/~sabedon/biol3025.htm

• Most DNA viruses are double-stranded (dsDNA) • Replicated in nucleus of

eukaryotic host cell

• Most RNA viruses are single-stranded (ssRNA) • Replicated in the host cell’s

cytoplasm

• Replication in cytosol is error-prone • high rates of mutation

• difficult targets for immune system and vaccines/drugs

15 http://www.nature.com/nrmicro/journal/v4/n5/box/nrmicro1389_BX1.html

Viral Genomes

• RNA viruses

• Positive-strand virus – viral RNA serves as mRNA

• Negative-strand virus – genome is complementary to the viral mRNA

• Retroviruses (HIV) employ reverse transcriptase to reverse transcribe viral RNA into DNA


Viral Genomes

Bacteriophage

• Viruses that infect bacteria • Diverse and united only by

bacterial hosts • Called “phage” for short • E. coli-infecting viruses are the

best studied – Include the “T” series (T1, T2, etc.)

• Viruses have also been found in archaea – Different from bacterial viruses – Characterization in early stages

19 http://fineartamerica.com/featured/bacteriophage-t4-virus-group-1-russell-kightley.html

Bacteriophages T4

virus infecting E. coli

Reproductive cycles Bacteriophages • Attachment or adsorption

– Target part of bacterial outer surface

– Recognition of appropriate host

• Penetration or injection – T4 pierces cell wall to inject

viral genome

• Synthesis – Phage may immediately take

over the cell’s replication and protein synthesis enzymes to synthesize viral components

20 http://www.nature.com/scitable/content/a-schematic-of-the-lifecycle-of-a-35875

• Assembly – Assembly of components

• Release – Mature virus particles are released

through enzyme that lyses host or budding through host cell wall

• Eclipse period – Time between adsorption (first

entering cell) and the formation of new viral particles

– If a cell is lysed at this point, few if any active virions can be released

21

http://www.nature.com/scitable/content/a-schematic-of-the-lifecycle-of-a-35875

• Lytic cycle • Virus lyses infected host cell

• Virulent or lytic phages

• Lysogenic cycle • Virus does not immediately

kill infected cell

• Integrates viral nucleic acid into host cell genome – prophage

• Integration allows a virus to be replicated along with the host cell’s DNA as the host divides

• Temperate or lysogenic phage


• Binal phage lambda (λ) of E. coli – Best studied biological

particle

– When phage λ infects a cell, the early events constitute a genetic switch that will determine whether the virus is lytic or lysogenic

– Induction during stress • Prophage can be excised

and begins lytic cycle

• Requires turning on the gene expression necessary for the lytic cycle

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genetic switch

• Phage conversion • Phenotype or characteristics of

the lysogenic bacterium is altered by the prophage • Due to viral DNA inserted into

host genome

• Vibrio cholerae phage conversion • Lysogenic phage introduced a

gene coding for cholera toxin

• Gene became incorporated into host genome

• Converts harmless bacteria into disease-causing form

25 http://www.pnas.org/content/105/33/11951/F3.expansion.html

Human Immunodeficiency Virus

• HIV causes acquired immune deficiency syndrome (AIDS)

• AIDS was first reported in the U.S. in 1981

– Origin in Africa in 1950s

• Some people are resistant to HIV infection

– Exposed repeatedly never become positive

– Others become HIV-positive without developing AIDS

– Others have little resistance and progress rapidly from infection to death

26

HIV (green)

budding from a

lymphocyte, SEM

http://en.wikipedia.org/wiki/HIV/AIDS

• Variability in resistance may be due to selective pressure by smallpox virus

• Before its eradication, smallpox killed billions

• Individuals without smallpox receptor were resistant to smallpox

• CCR5 receptor used by HIV may have been used by smallpox

• Therefore those resistant to smallpox also resistant to HIV

• Historical appearance and distribution of CCR5 mutation correlates with historic distribution of smallpox

27

Left: Role of CCR5 protein

in recognition/entry of HIV

into host cell.

Right: Frequencies of

mutant CCR5 allele are

higher in European

populations, which tend to

be more resistant to HIV.

http://evolution.berkeley.edu/evolibrary/news/081001_hivmalaria http://www.medscape.com/viewarticle/705842_3

• HIV targets CD4+ cells, mainly helper T cells

– Without these cells, the body cannot mount an effective immune response

– Host may ultimately die from a variety of opportunistic infections that do not normally cause disease

• Clinical symptoms of AIDS usually appear after 8–10 year latent period

– Provirus integrates in genome of macrophages and CD4+ cells

28

http://classes.midlandstech.edu/carterp/Courses/bio225/chap19/lecture8.htm

http://www.journaids.org/index.php/essential_information/hivaids_overview/

• HIV testing – Not a test for circulating virus

– Test for presence of antibody against HIV

– Further testing confirms HIV-positive status

• Spread of AIDS – Carriers have no clinical

symptoms but are infectious

– Infection continues throughout latent period

– Mutation allows the virus to overcome immune system and AIDS begins

29 http://www.thebody.com/content/art17197.html

HIV Infection Cycle

• Model for animal viruses • Details may vary for other

viruses

• Attachment (1) • Virus only attacks CD4+ cells

• Viral gp120 attaches to CD4 protein on macrophages and CD4+ cells

• Coreceptors like CCR5 affect likelihood of entry

• Entry through fusion pore (2)

30 http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/pages/hivreplicationcycle.aspx

• Replication – Reverse transcriptase converts

virus RNA to double-stranded DNA (3) • Mutations common in process

– DNA is incorporated into host genome (4)

– Variable period of dormancy

• Assembly (5) • Making many copies of virus

• Release (6) • New viruses exit by budding

31

http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/pages/hivreplicationcycle.aspx

AIDS treatments • FDA lists 32 antiretroviral drugs used in AIDS therapy

• Targets four aspects of HIV life cycle – Blocking viral entry (CCR5)

– Interfering with genome replication (AZT blocks reverse transcription)

– Block integration of viral DNA (integrase inhibitor)

– Maturation of HIV proteins (protease inhibitors)

33

• Vaccine development has been unsuccessful

– Problem had been seen as high mutation rate

– Real problem is no vaccine yet has produced strong cellular immune response

– Attenuated SIV vaccine

• Mutated back into infective virus

• Experimental animals developed simian AIDS

34 http://2007.igem.org/Ljubljana/AIDSplague

Influenza • One of the most lethal viruses in

human history • 20–50 million people died worldwide

between 1918 and 1919

• Flu viruses are enveloped animal viruses

• 3 “types” based on capsid protein • Type A - Serious epidemics in humans

and other animals

• Types B and C – Mild human infections

• Subtypes differ in protein spikes • Hemagglutinin (H) – Aids in viral entry

• Neuraminidase (N) – Aids in viral exit 35

http://en.wikipedia.org/wiki/Influenza

• H and N molecules accumulate mutations (drift)

– Thus we have yearly flu shots, and not a single vaccine

– Type A viruses are classified into 13 distinct H subtypes and 9 distinct N subtypes

• Flu viruses can also undergo genetic recombination when 2 subtypes infect the same cell (shift)

– Creates novel combinations of spikes unrecognizable by human antibodies

36

http://www.petpigs.com/resources/2009-h1n1-influenza-

pandemic/novel-influenza-a-h1n1

• Antigenic shifts (exchange between types) have caused pandemics – Spanish flu of 1918, A(H1N1)

• Killed 20–50 million worldwide

– Asian flu of 1957, A(H2N2) • Killed over 100,000 Americans

– Hong Kong flu of 1968, A(H3N2) • Infected 50 million in U.S., killing

70,000 37

Antigenic shift

Original influenza virus New strain of virus

H antigen

N antigen

New H antigen

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Antigenic drift

(mutation)

Antigenic shift

(recombination)

http://jbiol.com/content/8/5/46/figure/F1?highres=y

• New strains of flu often originate in the Far East

• Virus hosts are ducks, chickens, and pigs • In Asia, livestock often live in

close proximity to each other and humans

• Simultaneous infection with different strains favors genetic recombination (antigenic shift) • Hong Kong flu arose from

recombination between a duck and human version

38

Antigenic drift

(mutation)

Antigenic shift

(recombination)

http://jbiol.com/content/8/5/46/figure/F1?highres=y

Emerging Viruses

• Viruses that extend their host range

• Often deadly to new host • Considerable threat in the

aviation age – You can “jump” continents on

an airplane before knowing you are ill

• Hantavirus – Causes deadly pneumonia – Natural host is deer mice – Controlling deer mice has

limited disease

39

http://www.sfgate.com/health/article/Hantavirus-outbreak-puzzles-experts-3888327.php

https://ufhealth.org/hantavirus

• Ebola virus

• Causes severe hemorrhagic fever

• Among most lethal infectious diseases

• Host is unknown

• SARS

• Severe acute respiratory syndrome

• Caused by a coronavirus

• Host is civet (weasel-like)

• Mutation rate low compared to HIV

• SARS vaccines currently being developed

40

0.3 µm


© Corbis/Volume 40 RF; pp. 537-538: © Dr. Gopal Murti/Visuals Unlimited


E M

S

RNA

N

SARS genes

RA RB S E M N

Viruses and Cancer • Viruses may contribute to about

15% of all human cancers

• Viruses can cause cancer by altering the growth properties of human cells – Triggering expression of

oncogenes – Disrupt cell cycle control genes

• In June 2006, FDA approved use of a new HPV vaccine to prevent cervical cancer – Administered to women and

young girls over the age of 11 to prevent cervical cancer

41 http://www.mediahex.com/Council_for_Mutual_Economic_Assistance

Prions • “Proteinaceous infectious particles”

• Cause transmissible spongiform encephalopathies (TSEs) – as neurons die, spaces are left causing spongy appearance

– “Mad cow” disease – BSE

– Scrapie in sheep

– Creutzfeldt–Jacob disease in humans (CJD)

• Host has normal prion proteins (PrPc) – Misfolded proteins (PrPsc) cause

disease

– Misfolded prions may cause normal proteins to misfold

42

http://wonderfulpants.wordpress.com/diseases/prion-disease/

http://faculty.southwest.tn.edu/rburkett/viruses_and_prions.htm

43

Normal PrP protein is necessary for productive

infection by scrapie infectious particle.


Brain homogenate

Control mouse

Scrapie

infected

mouse

Mice die of neurological

disorder. Brain sections

show characteristic damage.

Mice live normal life span.

Brain appears normal.

PrP deletion

mouse

Viroids • Tiny naked molecules of circular

RNA that infect plants

• Cause diseases in plants – Recent outbreak killed over 10

million coconut palms in the Philippines

• Autonomously replicate – Info appears to be in 3-D

structure and not RNA

– Might use plant siRNA (small interfering RNA) machinery to affect gene expression (e.g. post-transcriptional gene silencing)

44 http://theses.ulaval.ca/archimede/fichiers/21404/ch03.html

http://biopolyverse.com/2011/05/03/does-%E2%80%98dark%E2%80%99-biology-have-its-charms/